Action Points

Explain to interested patients that the data reported here describe response to a therapy that is not currently available.

This study was published as an abstract and presented in a poster at a conference. These data and conclusions should be considered to be preliminary as they have not yet been reviewed and published in a peer-reviewed publication.

LOS ANGELES, May 23 â€” Patients with moderate to severe Crohn's disease had a significant response to initial infusion with Tysabri (natalizumab) and then at eight weeks, researchers said here.

In the results of the ENCORE trial, reported at Digestive Disease Week sessions, 51% of patients receiving Tysabri responded to the initial infusion versus 37% of patients in the placebo group (P=0.001). At eight weeks the difference was still significant, with 48% of Tysabri patients showing a response versus 32% of the placebo group (P<0.001).

And significantly more patients in the Tysabri group achieved clinical remission (defined as reduction of at least 150 points in the Crohn's Disease Activity Index score) at eight and 12 weeks (26% versus 16%, P=0.002), said Stephan Targan, M.D., of the University of California at Los Angeles and director of the inflammatory bowel disease center at Cedars-Sinai Medical Center.

Dr. Targan said the response and remission rates for Tysabri were superior to placebo at all time points beginning at week four (P<0.001), which confirms the efficacy of Tysabri as induction therapy.

ENCORE (Efficacy of Natalizumab in Crohn's Disease Response and Remission) was a phase III trial that enrolled 510 patients with a CDAI score between 220 and 450 and C-reactive protein levels of more than 2.87 mg/L (upper limit of normal). Two hundred and fifty-nine patients were randomized to Tysabri infusions at baseline, week four, and week eight, and 250 to placebo.

The primary endpoint was a decrease in CDAI score of 70 points or more by week eight that was sustained through week 12.

Maria T. Abreu, M.D., of Mount Sinai in New York, said one of lingering concerns about Tysabri has been whether it would work quickly. "As a clinician, my concern is simple: if I give this drug to my patients will it work and work quickly. These data indicate that it would."

Dr. Abreu chaired a DDW press briefing where the ENCORE results were outlined.

Tysabri, which is a humanized IgG4 monoclonal antibody, first took off as a treatment for multiple sclerosis and generated considerable enthusiasm as a potential treatment for Crohn's disease and rheumatoid arthritis. But that enthusiasm was quickly dampened in February 2005 when the agent was voluntarily withdrawn from the market after three patients developed progressive multifocal leukoencephalopathy (PML).

A subsequent safety evaluation that included 1,275 Crohn's patients as well as 2,248 MS patients and 296 rheumatoid arthritis patients treated with Tysabri before it was withdrawn from the market put the risk of PML at 0.1%.

Moreover, all three patients who developed PML were also receiving concomitant immune modulation therapy, said William Sandborn, M.D., of the Mayo Clinic in Rochester, Minn. Dr. Sandborn reported on the results of the Tysabri safety evaluation at DDW.

"Immune-modulation is the common theme in the PML story. So it is likely that if this drug comes back to the market that it will be used as monotherapy until this is better understood," Dr. Sandborn said.

On March 8, 2006, the Peripheral and Central Nervous System Drugs Advisory Committee of the FDA voted unanimously to recommend reintroduction of Tysabri as a treatment for relapsing forms of MS. Elan and Biogen Idec, makers of Tysabri said the FDA is expected to act on that recommendation by June 28.

But Dr. Targan cautioned that if Tysabri returns to the market "it will return with an indication for MS. Use of the drug for Crohn's disease will be off-label until the FDA approves that indication." Given the previous safety concerns he predicted that there may be restrictions that would limit such off-label use.

Reviewed by
Rubeen K Israni, MD, Fellow, Renal-Electrolyte and Hypertension Division, University of Pennsylvania School of Medicine